Abstract
BackgroundThe secretin family is a pleotropic group of brain-gut peptides with affinity for class 2 G-protein coupled receptors (secretin family GPCRs) proposed to have emerged early in the metazoan radiation via gene or genome duplications. In human, 10 members exist and sequence and functional homologues and ligand-receptor pairs have been characterised in representatives of most vertebrate classes. Secretin-like family GPCR homologues have also been isolated in non-vertebrate genomes however their corresponding ligands have not been convincingly identified and their evolution remains enigmatic.ResultsIn silico sequence comparisons failed to retrieve a non-vertebrate (porifera, cnidaria, protostome and early deuterostome) secretin family homologue. In contrast, secretin family members were identified in lamprey, several teleosts and tetrapods and comparative studies revealed that sequence and structure is in general maintained. Sequence comparisons and phylogenetic analysis revealed that PACAP, VIP and GCG are the most highly conserved members and two major peptide subfamilies exist; i) PACAP-like which includes PACAP, PRP, VIP, PH, GHRH, SCT and ii) GCG-like which includes GCG, GLP1, GLP2 and GIP. Conserved regions flanking secretin family members were established by comparative analysis of the Takifugu, Xenopus, chicken and human genomes and gene homologues were identified in nematode, Drosophila and Ciona genomes but no gene linkage occurred. However, in Drosophila and nematode genes which flank vertebrate secretin family members were identified in the same chromosome.ConclusionsReceptors of the secretin-like family GPCRs are present in protostomes but no sequence homologues of the vertebrate cognate ligands have been identified. It has not been possible to determine when the ligands evolved but it seems likely that it was after the protostome-deuterostome divergence from an exon that was part of an existing gene or gene fragment by rounds of gene/genome duplication. The duplicate exon under different evolutionary pressures originated the chordate PACAP-like and GCG-like subfamily groups. This event occurred after the emergence of the metazoan secretin GPCRs and led to the establishment of novel peptide-receptor interactions that contributed to the generation of novel physiological functions in the chordate lineage.
Highlights
The secretin family is a pleotropic group of brain-gut peptides with affinity for class 2 G-protein coupled receptors proposed to have emerged early in the metazoan radiation via gene or genome duplications
The present study focuses on secretin family ligands and complements previous studies aimed at identifying and characterising the evolution of family 2 (G-Protein Coupled Receptors) (GPCRs) [5,6,8,14,17]
A vasoactive intestinal peptide (VIP) and GCG peptides were isolated from the Alligator mississippiensis, the nucleotide precursor of the latter peptide reported from the Heloderma suspectum [28,29,30] and a PACAP-related peptide (PRP)/(Pituitary Adenylate Cyclase-Activating Polypeptide) (PACAP) mRNA was recently characterised from the Italian wall lizard Podarcis sicula [31,32]
Summary
The secretin family is a pleotropic group of brain-gut peptides with affinity for class 2 G-protein coupled receptors (secretin family GPCRs) proposed to have emerged early in the metazoan radiation via gene or genome duplications. Secretin-like family GPCR homologues have been isolated in non-vertebrate genomes their corresponding ligands have not been convincingly identified and their evolution remains enigmatic. Class 2 GPCRs is a larger family of receptors and includes members of the metazoan adhesion (B2) and insect methuselah (B3) families and secretin family GPCRs (B1) are proposed to descend from the adhesion receptors prior to protostome-deuterostome divergence [5,6]. In protostomes with fully sequenced genomes and extensive molecular resources (Figure 1, Additional file 1), genes encoding ligands homologous to members of the vertebrate secretin family have not been reported. Secretin-like family GPCR encoding genes which share similar sequence, structure and conserved gene environment with the vertebrate members have been identified, making ligand-receptor evolution an interesting enigma [13,14,15,16]
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